CHOC Children’s Hospital recently administered the first ever in-human dosing
of gene therapy for Hurler Syndrome, the severe form of mucopolysaccharidosis
type I (MPS I), a rare and progressive lysosomal storage disease.
successful, the gene therapy could present an alternative treatment for Hurler
Syndrome, which currently calls for a stem cell transplant for children younger
than 2 ½. While stem cell transplants are well-proven to help prevent most of
the neurologic decline that happens to untreated MPS I patients, the procedure
poses significant risks.
Patients with MPS I have a
genetic mutation that leads to a deficiency in alpha-L-iduronidase. This enzyme
helps break down chemicals called glycosaminoglycans, specifically dermatan and
heparin sulfate, the buildup of which can ultimately cause enlarged organs and
tissues, heart valve thickening, spinal cord compression, hydrocephalus and progressive
loss of intellectual milestones.
The hope is that the gene therapy – RGX-111, which is produced by REGENXBIO Inc. – will equip the patient’s brain cells with the information needed to make working alpha-Liduronidase enzyme to stop the glycosaminoglycans from building in the brain, says Dr. Raymond Wang, a CHOC pediatric metabolic disorders specialist and the study’s lead investigator.
The therapy was
administered through a cervical puncture in the neck. With three-dimensional
visualization and guidance from a computed tomography scanner, CHOC
interventional radiologist Dr. Tammam Beydoun carefully inserted the needle into
the fluid-filled space at the junction of the spinal cord and brain stem. Then,
Dr. Wang administered the gene therapy.
“I could not have
asked for a better implementation of everything we had planned for many months,”
Dr. Wang says. “I am so grateful for such an awesome team of people working
together for one common goal.”
Dr. Wang says the patient will be monitored indefinitely, with clinicians tracking the child’s cognitive and physical development, as well as measuring the quantity of alpha-L-iduronidase in the child’s body and spinal fluid to determine whether glycosaminoglycans dermatan and heparin sulfate are being broken down.
“I cannot guarantee if the
gene therapy is going to work, but the alternative was to watch and let this
patient get worse and worse and worse,” said Dr. Raymond Wang. “We’ve got to
Babies with MPS I show no
signs of the condition upon birth. To this end, MPS I was added to the list of
conditions tested for in California’s Newborn Screening Program in 2018. But
even with enzyme replacement therapy treatment, recommended to begin before age
2, the disease continues to progress, Dr. Wang says.
“Patients will reach a plateau in developmental milestones, and then they’ll start losing milestones,” he says. “Once they could speak, they lose the ability to speak. Once they were able to walk, they lose ability to walk. Then it gets to be really heartbreaking: Once they could eat, then they can’t eat anymore.”
Many patients ultimately rely
on feeding tubes, while often enduring airway problems, cardiac disease and
hydrocephalus. Quality of life is typically poor, Dr. Wang says.
Not only could a
successful outcome in this investigation dramatically change the course of a
patient’s life, but it could also pave the way for future gene therapy for
additional patients with rare diseases at CHOC, Dr. Wang says.
“This is an opening chapter for a very cool story,” Dr. Wang says.
Christine Schweer knew early on that her son, Colten, faced
some health complications.
Christine, a pediatric intensive care nurse living in the
Midwest with her husband, Todd, and then 3-year-old daughter, Chloe, recalls
feeling different during her pregnancy with Colten. Once Colten was born,
little things started popping up, she says.
Over the next few months, Colten developed several symptoms:
cold hands and feet, a sleepy demeanor, strange breathing and chronic, involuntary
eye movements – a condition called nystagmus.
At this point, Colten had already gone through several emergency department visits, including an admission to the hospital for respiratory syncytial virus (RSV) and eventually unexplained heart failure. But after genetic testing and screening for cystic fibrosis, cancer and blood clots all came back negative, Colten and his parents and doctors were left confused.
Searching for an answer
Colten was 6 months old when two new symptoms arose. An
occupational therapist thought Colten’s vision and hearing were waning, and an
ophthalmologist confirmed the therapist’s suspicion.
Then, around 9 months old, Colten’s weight mysteriously began
Meanwhile, the Schweers decided to relocate to California to
be near family. Christine, who now works in the PICU at CHOC Children’s at
Mission Hospital, transferred all of Colten’s records to CHOC. She began to
schedule visits to a team of CHOC providers, including pediatrician Dr. Lauren
Dwinell and pediatric cardiologist Dr. Anthony
Armed with her signature beach bag full of Colten’s records,
Christine continued the search for a diagnosis with Colten’s new care team, led
by Dr. Chang.
“We hit it off right away,” Christine says of Dr. Chang. “He
admired me for my dedication and advocacy for Colten, and I respected him for
his thoroughness, for trusting my parental instincts and for his commitment to
innovative treatment. We developed a good rapport and a lot of trust. He would
listen to me and recommend next steps for us both; then we would meet and
But the Schweers and Dr. Chang were still puzzled by
Colten’s symptoms, and Colten was now 2 years old.
“Nothing was adding up,” Christine says. Colten’s heart
function would worsen if off his medication, and his weight continued to climb.
“He was eating healthy and walking, swimming and exercising a lot, but his
weight was not budging.”
A few years passed while they continued to search for an answer.
An answer at last
Dr. Chang suggested they revisit genetic testing, despite
Colten having received genetic testing a few years prior.
“We trusted Dr. Chang’s instinct,” Christine says. “He
pointed out that tests can change even in a short time, and he wanted to be
sure we covered our bases.”
He sent them to Dr. Neda Zadeh,
a CHOC pediatric geneticist and Associate Director of the Molecular Diagnostic
A thorough walkthrough of Colten’s history and several
questions later, Dr. Zadeh had an idea. Recalling a case she encountered during
her fellowship at Stanford University, she brought up a rare condition called Alström
Syndrome and suggested they test for it.
While they waited, Christine got to work researching Alström Syndrome symptoms and immediately knew they had figured it out.
“Alström checked all the boxes: heart failure, flat and wide
feet, nystagmus, obesity and delayed developmental milestones – it completely
fit,” Christine says.
Six months later, a genetic sequencing test paid for by the foundation Alström Syndrome International confirmed what Christine and Dr. Zadeh suspected – Colten had Alström Syndrome. He was the 972nd person in the world to receive the rare diagnosis. By this point, he was 8 years old.
The Schweers were immediately welcomed into the Alström
family, Christine says. They got involved with the foundation that covered
Colten’s genetic testing, and families around the country and globe reached out
to them. Colten even met one of his current best friends, a boy with Alström
Despite the relief of a diagnosis after years of searching, Alström
came with some difficulties. The diagnosis meant that Colten’s vision was weak
and that his hearing would decline, too. The disease also affects his lungs,
kidneys, liver and weight.
“It of course felt horrible at first to me and my husband to
learn that Colten has a rare disease, but it was also a relief to know that we
had an answer now; there wouldn’t be so many surprises anymore,” Christine recalls.
The Schweers continued to work with Colten’s specialists, finally certain they knew the cause of his symptoms.
Collaboration is key
Christine reflects on the years of searching for answers and, despite the difficult moments, feels thankful for their collaborative care team at CHOC.
“If it weren’t for Dr. Chang suggesting more genetic
testing, if he hadn’t advised we see Dr. Zadeh and if it weren’t for the Alström
case Dr. Zadeh remembered from years before, we probably wouldn’t have figured
it out,” she says.
Christine thanks Dr. Chang for always keeping innovation in
“It would be easy to think inside the box and rely on past
test results,” Christine says, “but Dr. Chang always stayed up-to-date with
tests and looked at things creatively. It’s a multidisciplinary team approach
Most importantly, Christine admires the way Colten’s care
team relates with him.
“Doctors at CHOC are very personal with Colten,” she says.
“They get on his level and take time to get to know him and what he’s been up
to. Colten trusts them and wants to make them happy, so it’s always a positive
experience for him to see them.”
The approach has resulted in a fruitful partnership between Colten,
his parents and his providers.
“We’re all such a good team now. We feel confident we’re
doing everything we can possibly be doing for Colten.”
Learning about rare
disease at Peds2040
The experience getting Colten’s diagnosis sparked in
Christine a connection to the rare disease community. She heard about a rare
disease panel planned for the Pediatrics 2040
Conference, an annual conference on innovation in pediatrics spearheaded by
Dr. Chang, who had since been appointed CHOC’s Chief Innovation Officer and
head of CHOC’s Sharon
Disney Lund Medical Intelligence and Innovation Institute (MI3). Christine expressed
interest in attending right away, so MI3 sponsored her to attend. The
experience was invaluable.
“It was a great learning opportunity,” Christine says. “I
had lunch with a speaker whose son had a rare cancer, spoke with other families
and shared Colten’s story with providers, interns and residents.”
Thinking back to Colten’s journey to a diagnosis, Christine
felt grateful they had MI3 and Dr. Chang on their side. Peds2040 highlights the
importance of medical innovation to those with rare diseases.
One of the most memorable moments of the conference for Christine was Colten arriving toward the end of the day, when he was able to catch up with Dr. Chang.
Today, Colten is a loving, strong-willed, intelligent
13-year-old with a deep love of cars and an amazing memory. These days, he and
his family are grateful to be able to go several months between specialist
Even so, Christine notes, he faces some difficulties.
He is short for his age, so they’re seeing endocrinologist Dr. Himala Kashmiri to monitor his hormone levels. Additionally, like his vision, Colten’s hearing has waned and will continue to weaken during his teenage years. But, Christine reports, he has learned braille and thriving at it. And, because Alström can affect multiple organs, they continue to watch his heart, liver and kidney function with the help of medication and several specialists.
Colten continues to see Drs. Dwinell and Chang, along with nephrologist Dr. Shoba Narayan, pulmonologist Dr. Chana Chin, gastroenterologist Ellen Schoenfield, NP, registered dietitian Vanessa Chrisman, audiologist Dr. Kristi Panek and a pediatric ophthalmologist.
Nevertheless, the Schweers ensure Colten is empowered to do
what he wants.
“We’ve never held him back from doing something,” Christine
says. “If he wants to do something, we’re going to make it happen.”
Colten joined a Challenger baseball team for kids with
special needs, now one of his favorite activities.
And, despite vision loss, his love of cars is as strong as
“Before, he could instantly tell you what a car was when he
saw it” Christine says. “Now, he can identify them by sound.”
Some of Colten’s favorite memories so far include joining
his baseball team, going horseback riding and ziplining, and he has plenty more
“Despite his challenges, he’s very determined and has a
don’t-baby-me, I-can-do-this attitude that impresses me – and makes me a
nervous wreck,” Christine adds.
“When Colten was little, his doctors said he might not be able to talk. Now we joke that we have to beg him for five minutes of quiet. He doesn’t stop talking when he’s around his loved ones.”
Advice for other
Christine looks back at the difficult road to a diagnosis
and is now grateful for the community that Alström has brought her family.
“Let yourself grieve after a difficult diagnosis,” she says, “but also try to recognize you’re part of a new family. You’re not alone in this. Know that there are other parents out there who know what this feels like, so don’t try to take it on all by yourself. Despite how it can feel at first, every day is not going to be a bad day.”
For many children undergoing
tonsillectomies at CHOC Children’s, gone are the weeks missing school, a liquid
diet and powerful narcotic painkillers.
Instead, a new technique for tonsillectomies practiced at CHOC means patients return to school and a regular diet sooner and require only over-the-counter pain medication such as Tylenol.
More importantly, the risk for
potentially life threatening post-operative bleeds – 3 to 8 percent in
traditional tonsillectomies – and hospital readmissions drop dramatically when
children undergo procedures using this technique.
intracapsular tonsillectomy, the surgeon deftly shaves away at the tonsil,
leaving a small portion (the outer wall called the capsule) behind. In
contrast, a traditional total tonsillectomy removes the entire organ, exposing raw muscle and blood vessels behind the tonsil, which
increases pain and bleeding risk.
Due to the significant benefit
to patients, the technique has become routine at CHOC. These physicians are
working to raise awareness about this technique in the community, as well as with
their physician peers nationwide.
Drs. Huoh and
Pham learned the intracapsular technique as fellows, but for years practiced
the traditional tonsillectomy version they learned as residents, they
But a few years after joining CHOC, they made a change. Drs.
Huoh and Pham lamented the number of patients
complaining of pain after surgery; the number of narcotic pain prescriptions
they wrote; and the number of patients returning to the hospital post-surgery
with dehydration, pain and bleeding.
After largely switching to the intracapsular
technique, they’ve had zero bleeds after more than 1,000 procedures – and,
anecdotally, they have happier patients.
For example, Jenna Opp underwent
the new procedure with Dr. Pham about nine months ago as a high school senior.
Her mother had also undergone a
tonsillectomy as a teenager and prepared Jenna for the worst. But after the surgery, Jenna drank a
smoothie and by that night, she enjoyed eggs and French toast for dinner. Two
days later she was back in school and craving a hamburger.
The experience was an about-face
from her mother’s memories of weeks of pain coupled with a steady oatmeal diet.
And even better – after a lifetime of chronic bouts of strep throat, Jenna has
been healthy ever since.
“They offered to do it the old way or the new way,” Jenna says. “They told me the new procedure is way less painful and only takes a couple of days for recovery. I was like, ‘I’m sold on that,’ and it was awesome.”
Here are some keys things to
know about the intracapsular tonsillectomy technique:
The tonsil regrowth rate following an intracapsular
tonsillectomy at CHOC is 0.5 to 1%.
The procedure takes the same amount of time as a traditional
tonsillectomy – 30 to 45 minutes.
Intracapsular tonsillectomy is growing in popularity in the
United States. Elsewhere in the world, such as in Sweden and France, it’s the
preferred method of tonsil removal.
Usually children will require only over-the-counter pain
medication such as Tylenol for a few days after surgery. Some children do not
require any pain medication.
There are no age restrictions for this procedure.
more about referring a
patient to CHOC’s otolaryngologists.
Children’s nurse scientist will discuss the health system’s culture of
collaborative innovation this month at a prestigious Cleveland Clinic
conference, marking the first time outside organizations have been invited to
Hayakawa, DNP, CNS, CCRN, CNRN, will participate in a panel discussion titled
“Teamwork makes the dream work” at the seventh annual Nursing Innovation Summit on Oct. 23.
presentation, “Defending Childhood Through Collaborative Innovation,” Jennifer
will discuss the role of a nurse scientist; CHOC’s infrastructure to support
nurse innovation; and CHOC nurses’ collaboration with multidisciplinary teams while
in pursuit of innovation.
Multidisciplinary collaboration at
To illustrate the multidisciplinary collaboration at CHOC, Jennifer will also highlight a nurse-led innovation to study pediatric outcomes on a medical device that has been primarily used in adults. CHOC is among the first institutions worldwide to study the use of automated pupillometry in pediatrics. Pupillometers provide reliable and objective data to assist with early detection of subtle neurological changes.
pupillometry has been integrated into standard of care and clinical
decision-making in adult intensive care units across the nation,” Jennifer
says. “While there are multiple studies that validate the use of pupillary
metrics to improve clinical outcomes in adult populations, there are very few
published studies describing its use in children. Several children’s hospitals
are using it, but we’re the first to develop a robust database. Through that,
we’ve learned more about what works for our population and we have identified a
few challenges unique to pediatrics.”
The idea to begin collecting this data came from the pediatric intensive care unit nurses at CHOC – and has led to a valued partnership with the device manufacturer. Through that relationship, a CHOC multidisciplinary research team will soon begin evaluating the use of pupillary metrics in the assessment and management of concussion, Jennifer says.
help our industry partner to improve their product and will allow us to learn
more about application of this new technology in diverse clinical populations,”
she says. “We collaborated with the CHOC Research Institute and Innovation Lab to connect with lawyers to get advice about intellectual
property and data use agreement contracts. That’s the focus of the conference
and panel – working together to innovate healthcare – navigating all of those
panel, Jennifer will share the stage with a physician and a patent attorney,
and she’s thrilled for the opportunity.
collaboratively to innovate care is something I’m really passionate about,” she
The path to a research career
path toward becoming a nurse scientist at CHOC began about 18 years ago, when
she joined the organization as a unit secretary while in nursing school. Upon
graduation, Jennifer began work at the bedside in the pediatric intensive care
years, she transitioned to an educator role and later to a clinical nurse
specialist role. About two years ago, Jennifer
became CHOC’s nurse scientist.
thought I’d move away from the bedside,” she says. “But my career path and
professional growth has led to different opportunities.”
knew research was an important part of my role as a clinical nurse specialist,
but research always seemed daunting” she says. “Coming out of that program
changed my perspective and gave me the confidence to pursue my doctorate
Research isn’t done in a silo
In her role
today, Jennifer is charged with nurturing a culture of inquiry at CHOC.
Critical to that is building infrastructure, while also mentoring and guiding
nurses through the research process.
incorporates her experience as an intimated nascent researcher when working
today with nurses considering an investigation or embarking upon a new project.
“I tell them
they don’t have to do it alone,” she says. “Research and innovation isn’t done
in a silo; it’s done through a lot of multidisciplinary collaboration.”
As the role
nurses play in CHOC’s culture of inquiry continues to deepen, the results are
evident: In fiscal year 2019, CHOC nurses presented 31 posters and 24 podium presentations
at local and national conference and published five articles in peer-reviewed
“Research is integral to the care we provide at CHOC Children’s,” Jennifer says. “For families, it represents hope – hope for improved quality of life, hope for a cure, or hope to help other children and their families. It is an honor and a privilege to be a part of a team of talented people providing this innovative care.
Children’s Hospital has been designated a Diagnostic Imaging Center of
Excellence® (DICOE) by the American College of Radiology (ACR).
program, which represents the pinnacle of medical imaging care, is an
achievement that goes beyond accreditation to recognize best-quality imaging
practices and diagnostic care. This includes a comprehensive assessment of the
entire medical imaging enterprise, including structure and outcomes.
designation recognizes excellence at multiple levels — including the
professional staff, the technology and the policies and procedures the organization
follows — and superior patient care.
In order to
receive this elite distinction, facilities must be accredited by the ACR in all
modalities they provide, and in which the ACR offers an accreditation program. Another requirement
is to participate in the Dose Index Registry® and General Radiology Improvement
Database, as well as Image Wisely® and Image Gently®.
a full range of specialized pediatric imaging services, including ultrasound,
X-ray, fluoroscopy, MRI and CT scans.
that children don’t need adult levels of radiation, radiation doses on CHOC
equipment can be up to 50 percent lower than at community hospitals or
independent imaging centers.
only board-certified pediatric radiologists and specially trained pediatric
radiology technologists, nurses and child life specialists. Additionally, all
radiology staff undergo age-specific training annually to learn how to work and
communicate with children of varying ages.
is only one of a small number of medical centers in the country to have child
life specialists working in a dedicated pediatric radiology and imaging
founded in 1924, is one of the largest and most influential medical
associations in the United States. The ACR devotes its resources to making
imaging and radiation therapy safe, effective and accessible to those who need
it. Its 38,000 members include radiologists, radiation oncologists, medical
physicists, interventional radiologists and nuclear medicine physicians.